ABSTRACT
The design of powerful in vitro cell culture platforms to support precision medicine can contribute to predict therapeutic success of cancer patients. Electrospun nanofibers applied to cell culture can mimic extracellular matrix and improve in vitro cell behavior. Here, we describe biocompatible blended polyvinyl-alcohol (PVA)/gum arabic (GA) extracellular matrix (ECM)-like nanofibers for in vitro cell cultures capable of delivering nanocomposite for desired biomedical application. Therefore, PVA/GA ECM-like electrospun nanofibers were developed and characterized. Heat treatment was used to crosslink the nanofibers and biocompatibility was evaluated, which demonstrated the ability of developed platform to provide a cell culture-friendly environment. Previous work demonstrated that GA-gold nanoparticles (GA-AuNPs) in non-cytotoxic concentrations can reduce key metastatic cellular events such as invasion and colony formation of metastatic melanoma cells. Thus, crosslinked nanofibers were functionalized with GA-AuNPs and its cellular delivery was evaluated. GA-AuNPs were efficiently adsorbed onto the PVA/GA nanofibers surface and the system effectively delivered the nanocomposites to metastatic melanoma cells. In conclusion, the described biocompatible system could be prospected as a valuable in vitro tool for precision medicine.
Subject(s)
Biomimetics , Gum Arabic/chemistry , Nanofibers/chemistry , Nanomedicine , Polyvinyl Alcohol/chemistry , 3T3 Cells , Animals , Biocompatible Materials , Cell Adhesion , Cell Line, Tumor , Cell Proliferation , Cell Survival , Drug Delivery Systems , Extracellular Matrix/metabolism , Humans , Mice , Nanofibers/ultrastructure , NeoplasmsABSTRACT
Gold nanoparticle (AuNP)-based systems have been extensively investigated as diagnostic and therapeutic agents due to their tunable properties and easy surface functionalization. Upon cell uptake, AuNPs present an inherent cell impairment potential based on organelle and macromolecules damage, leading to cell death. Such cytotoxicity is concentration-dependent and completely undesirable, especially if unspecific. However, under non-cytotoxic concentrations, internalized AuNPs could potentially weaken cells and act as antitumor agents. Therefore, this study aimed to investigate the antitumor effect of ultrasmall AuNPs (~3 nm) stabilized by the anionic polysaccharide gum arabic (GA-AuNPs). Other than intrinsic cytotoxicity, the focus was downregulation of cancer hallmarks of aggressive tumors, using a highly metastatic model of melanoma. We first demonstrated that GA-AuNPs showed excellent stability under biological environment. Non-cytotoxic concentrations to seven different cell lines, including tumorigenic and non-tumorigenic cells, were determined by standard 2D in vitro assays. Gold concentrations ≤ 2.4 mg L-1 (16.5 nM AuNPs) were non-cytotoxic and therefore chosen for further analyses. Cells exposed to GA-AuNPs were uptaken by melanoma cells through endocytic processes. Next we described remarkable biological properties using non-cytotoxic concentrations of this nanomaterial. Invasion through an extracellular matrix barrier as well as 3D growth capacity (anchorage-independent colony formation and spheroids growth) were negatively affected by 2.4 mg L-1 GA-AuNPs. Additionally, exposed spheroids showed morphological changes, suggesting that GA-AuNPs could penetrate into the preformed tumor and affect its integrity. All together these results demonstrate that side effects, such as cytotoxicity, can be avoided by choosing the right concentration, nevertheless, preserving desirable effects such as modulation of key tumor cell malignancy features.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Gold Compounds/pharmacology , Melanoma, Experimental/drug therapy , Metal Nanoparticles , Skin Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/toxicity , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Stability , Endocytosis , Gold Compounds/chemistry , Gold Compounds/metabolism , Gold Compounds/toxicity , Gum Arabic/chemistry , Humans , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Mice , Nanomedicine , Neoplasm Invasiveness , Neoplasm Metastasis , Particle Size , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
Polyelectrolyte multilayer (PEM) capsules engineered with active elements for targeting, labeling, sensing and delivery hold great promise for the controlled delivery of drugs and the development of new sensing platforms. PEM capsules composed of biodegradable polyelectrolytes are fabricated for intracellular delivery of encapsulated cargo (for example peptides, enzymes, DNA, and drugs) through gradual biodegradation of the shell components. PEM capsules with shells responsive to environmental or physical stimuli are exploited to control drug release. In the presence of appropriate triggers (e.g., pH variation or light irradiation) the pores of the multilayer shell are unlocked, leading to the controlled release of encapsulated cargos. By loading sensing elements in the capsules interior, PEM capsules sensitive to biological analytes, such as ions and metabolites, are assembled and used to detect analyte concentration changes in the surrounding environment. This Review aims to evaluate the current state of PEM capsules for drug delivery and sensing applications.
Subject(s)
Capsules/chemistry , Drug Compounding , Models, Chemical , Polymers/chemistry , Biosensing Techniques , Chemical Phenomena , Drug Compounding/trends , Drug Delivery Systems , Mechanical Phenomena , Nanocapsules/chemistry , Nanotechnology/trendsABSTRACT
The self-assembly of polypeptides into stable, conductive, and intrinsically fluorescent biomolecular nanowires is reported. We have studied the morphology and electrical conduction of fibrils made of an elastin-related polypeptide, poly(ValGlyGlyLeuGly). These amyloid-like nanofibrils, with a diameter ranging from 20 to 250 nm, result from self-assembly in aqueous solution at neutral pH. Their morphological properties and conductivity have been investigated by atomic force microscopy, scanning tunneling microscopy, and two-terminal transport experiments at the micro- and nanoscales. We demonstrate that the nanofibrils can sustain significant electrical conduction in the solid state at ambient conditions and have remarkable stability. We also show intrinsic blue-green fluorescence of the nanofibrils by confocal microscopy analyses. These results indicate that direct (label-free) excitation can be used to investigate the aggregation state or the polymorphism of amyloid-like fibrils (and possibly of other proteinaceous material) and open up interesting perspectives for the use of peptide-based nanowire structures, with tunable physical and chemical properties, for a wide range of nanobiotechnological and bioelectronic applications.
